WASHINGTON – Yet another inhibitor of the Janus kinase enzyme has debuted with positive phase 2 results for patients with even longstanding alopecia areata.

Courtesy Concert Pharmaceuticals, Inc.

About half of those who took 8 mg of CPT-543, a chemically altered form of ruxolitinib, twice a day for 24 weeks, regrew hair – including eyebrows and eyelashes – by at least 50%. The dose-ranging study also found that a 4 mg twice-daily dose promoted the same growth in 21%, James V. Cassella, PhD, said during a late breaking clinical trials session at the annual meeting of the American Academy of Dermatology.

Adverse events were mild, including headache, reported in 26% of the 8 mg group. However, investigators “are keeping an eye” on infections and blood chemistry, and in light of the confirmed increased risk of herpes zoster and suspected increased risk of thromboembolic events with ??ruxolitinib, said Dr. Cassella, chief development officer of Concert Pharmaceuticals, which is developing the molecule.


Ruxolitinib, an inhibitor of both JAK1 and JAK2, is available under the name Jakafi and is approved for the treatment of myelofibrosis and polycythemia vera. The addition of deuterium slows its metabolism, increasing half-life and bioavailability without affecting receptor selectivity or potency, according to the company.

The company’s 24-week phase 2b study randomized patients with moderate to severe alopecia areata to CPT-543 at 4 mg twice daily (28), 8 mg twice daily (38), or placebo (35). The primary endpoint was the proportion of patients with at least a 50% relative reduction in scalp hair loss as measured by the Severity of Alopecia Tool (SALT) at 24 weeks, from baseline. Secondarily, the trial examined response by alopecia subtype (patchy or complete) and individual SALT changes compared with baseline.

Courtesy Concert Pharmaceuticals, Inc.

Courtesy Concert Pharmaceuticals, Inc.

Week 12 was the inflection point for response division, with both active groups significantly outperforming the placebo group. By week 16, 30% of the 8 mg group and about 15% of the 4 mg group had already hit the primary endpoint. Response in the 4 mg group climbed slowly until the end of the trial, while in the 8 mg group, response ascended more quickly. Response was still trending upward when the study stopped.

“We think we have not hit the ceiling effect with this drug,” Dr. Cassella said. “There is some evidence that response would continue to increase after 24 weeks.”

Patchy alopecia and alopecia universalis appeared to respond best to treatment in both dosage groups. There was no response in either group for patients with alopecia ophiasis or totalis.

Headache was the most common adverse event, and appeared to be dose-dependent, occurring in 11% of placebo patients, 17% of the 4 mg group, and 26% of the 8 mg group. Six patients developed increased blood creatinine phosphokinase levels (one in the placebo group, three in the 4 mg group, and two in the 8 mg group). There were no thromboembolic events. Three patients in the placebo group and two in the 8 mg group discontinued the medication due to unspecified adverse events.

In early March, the company announced an open-label dose-finding study, which will randomize 60 patients with moderate-to-severe alopecia areata to either 8 mg twice daily or 16 mg once daily over a 24-week treatment period. Concert intends to conduct a food-effect trial to assess the relative bioavailability of oral doses of CTP-543 under fasted and fed conditions in 14 healthy volunteers in the first half of 2019.

[email protected]

SOURCE: Casella J. AAD 2019; S034, Abstract 11291.

WASHINGTON – Yet another inhibitor of the Janus kinase enzyme has debuted with positive phase 2 results for patients with even longstanding alopecia areata.

Courtesy Concert Pharmaceuticals, Inc.

About half of those who took 8 mg of CPT-543, a chemically altered form of ruxolitinib, twice a day for 24 weeks, regrew hair – including eyebrows and eyelashes – by at least 50%. The dose-ranging study also found that a 4 mg twice-daily dose promoted the same growth in 21%, James V. Cassella, PhD, said during a late breaking clinical trials session at the annual meeting of the American Academy of Dermatology.

Adverse events were mild, including headache, reported in 26% of the 8 mg group. However, investigators “are keeping an eye” on infections and blood chemistry, and in light of the confirmed increased risk of herpes zoster and suspected increased risk of thromboembolic events with ??ruxolitinib, said Dr. Cassella, chief development officer of Concert Pharmaceuticals, which is developing the molecule.


Ruxolitinib, an inhibitor of both JAK1 and JAK2, is available under the name Jakafi and is approved for the treatment of myelofibrosis and polycythemia vera. The addition of deuterium slows its metabolism, increasing half-life and bioavailability without affecting receptor selectivity or potency, according to the company.

The company’s 24-week phase 2b study randomized patients with moderate to severe alopecia areata to CPT-543 at 4 mg twice daily (28), 8 mg twice daily (38), or placebo (35). The primary endpoint was the proportion of patients with at least a 50% relative reduction in scalp hair loss as measured by the Severity of Alopecia Tool (SALT) at 24 weeks, from baseline. Secondarily, the trial examined response by alopecia subtype (patchy or complete) and individual SALT changes compared with baseline.

Courtesy Concert Pharmaceuticals, Inc.

Courtesy Concert Pharmaceuticals, Inc.

Week 12 was the inflection point for response division, with both active groups significantly outperforming the placebo group. By week 16, 30% of the 8 mg group and about 15% of the 4 mg group had already hit the primary endpoint. Response in the 4 mg group climbed slowly until the end of the trial, while in the 8 mg group, response ascended more quickly. Response was still trending upward when the study stopped.

“We think we have not hit the ceiling effect with this drug,” Dr. Cassella said. “There is some evidence that response would continue to increase after 24 weeks.”

Patchy alopecia and alopecia universalis appeared to respond best to treatment in both dosage groups. There was no response in either group for patients with alopecia ophiasis or totalis.

Headache was the most common adverse event, and appeared to be dose-dependent, occurring in 11% of placebo patients, 17% of the 4 mg group, and 26% of the 8 mg group. Six patients developed increased blood creatinine phosphokinase levels (one in the placebo group, three in the 4 mg group, and two in the 8 mg group). There were no thromboembolic events. Three patients in the placebo group and two in the 8 mg group discontinued the medication due to unspecified adverse events.

In early March, the company announced an open-label dose-finding study, which will randomize 60 patients with moderate-to-severe alopecia areata to either 8 mg twice daily or 16 mg once daily over a 24-week treatment period. Concert intends to conduct a food-effect trial to assess the relative bioavailability of oral doses of CTP-543 under fasted and fed conditions in 14 healthy volunteers in the first half of 2019.

[email protected]

SOURCE: Casella J. AAD 2019; S034, Abstract 11291.

WASHINGTON – Yet another inhibitor of the Janus kinase enzyme has debuted with positive phase 2 results for patients with even longstanding alopecia areata.

Courtesy Concert Pharmaceuticals, Inc.

About half of those who took 8 mg of CPT-543, a chemically altered form of ruxolitinib, twice a day for 24 weeks, regrew hair – including eyebrows and eyelashes – by at least 50%. The dose-ranging study also found that a 4 mg twice-daily dose promoted the same growth in 21%, James V. Cassella, PhD, said during a late breaking clinical trials session at the annual meeting of the American Academy of Dermatology.

Adverse events were mild, including headache, reported in 26% of the 8 mg group. However, investigators “are keeping an eye” on infections and blood chemistry, and in light of the confirmed increased risk of herpes zoster and suspected increased risk of thromboembolic events with ??ruxolitinib, said Dr. Cassella, chief development officer of Concert Pharmaceuticals, which is developing the molecule.


Ruxolitinib, an inhibitor of both JAK1 and JAK2, is available under the name Jakafi and is approved for the treatment of myelofibrosis and polycythemia vera. The addition of deuterium slows its metabolism, increasing half-life and bioavailability without affecting receptor selectivity or potency, according to the company.

The company’s 24-week phase 2b study randomized patients with moderate to severe alopecia areata to CPT-543 at 4 mg twice daily (28), 8 mg twice daily (38), or placebo (35). The primary endpoint was the proportion of patients with at least a 50% relative reduction in scalp hair loss as measured by the Severity of Alopecia Tool (SALT) at 24 weeks, from baseline. Secondarily, the trial examined response by alopecia subtype (patchy or complete) and individual SALT changes compared with baseline.

Courtesy Concert Pharmaceuticals, Inc.

Courtesy Concert Pharmaceuticals, Inc.

Week 12 was the inflection point for response division, with both active groups significantly outperforming the placebo group. By week 16, 30% of the 8 mg group and about 15% of the 4 mg group had already hit the primary endpoint. Response in the 4 mg group climbed slowly until the end of the trial, while in the 8 mg group, response ascended more quickly. Response was still trending upward when the study stopped.

“We think we have not hit the ceiling effect with this drug,” Dr. Cassella said. “There is some evidence that response would continue to increase after 24 weeks.”

Patchy alopecia and alopecia universalis appeared to respond best to treatment in both dosage groups. There was no response in either group for patients with alopecia ophiasis or totalis.

Headache was the most common adverse event, and appeared to be dose-dependent, occurring in 11% of placebo patients, 17% of the 4 mg group, and 26% of the 8 mg group. Six patients developed increased blood creatinine phosphokinase levels (one in the placebo group, three in the 4 mg group, and two in the 8 mg group). There were no thromboembolic events. Three patients in the placebo group and two in the 8 mg group discontinued the medication due to unspecified adverse events.

In early March, the company announced an open-label dose-finding study, which will randomize 60 patients with moderate-to-severe alopecia areata to either 8 mg twice daily or 16 mg once daily over a 24-week treatment period. Concert intends to conduct a food-effect trial to assess the relative bioavailability of oral doses of CTP-543 under fasted and fed conditions in 14 healthy volunteers in the first half of 2019.

[email protected]

SOURCE: Casella J. AAD 2019; S034, Abstract 11291.

GLASGOW – Targeting circulating parasitic histones may hold promise for patients with cerebral malaria (CM), according to investigators.

A retrospective study, involving over 300 individuals, compared parasitic histone concentrations among patients with various forms of malaria and non-malarial illnesses, in addition to healthy controls, finding that elevated histone levels were associated with malarial disease severity and death, reported Simon Abrams, PhD, of the University of Liverpool, UK, a coauthor of the study. He noted that this research could guide the development of treatment strategies for hundreds of thousands of patients each year, particularly children.

“Cerebral malaria is the most severe form of Plasmodium falciparum infection, and despite effective anti-malarial therapy, between 10% and 20% of children that develop cerebral malaria die,” Dr. Abrams said during his presentation at the annual meeting of the British Society for Haematology. “This accounts for a huge amount of deaths per annum. Around 400,000 malarial deaths are in children in subSaharan Africa, and death typically occurs within 24 hours of hospital admission.”

In CM, the blood-brain barrier deteriorates, leading to brain swelling, hemorrhaging, clot formation, and in many cases, death, Dr. Abrams said. CM patients with the worst outcomes typically have retinal abnormalities on fundic exam, granting the disease subtype “retinopathy-positive.”

Aided by colleagues in Malawi, the investigators gathered over 300 patient samples for analysis. They found that patients with retinopathy-positive CM had higher mean extracellular histone levels than retinopathy-negative CM patients and healthy controls (22.6 mcg/ml, 6.31 mcg/ml, and 0.33 mcg/ml, respectively). In addition, retinopathy-positive CM patients who died had significantly higher levels of circulating histones, compared with similar patients who survived (35.7 mcg/ml vs. 21.6 mcg/ml).

These findings translated to predictive capability, as the investigators showed that patients with CM who had elevated histones when admitted to the hospital were at a higher risk of death than those with normal histone levels (P = .04). Unlike patients with CM, patients with uncomplicated malaria had relatively low histone levels (0.57 mcg/ml), as did patients with mild non-malarial febrile illness (1.73 mcg/ml) and non-malarial coma (1.73 mcg/ml).

During his presentation, Dr. Abrams elaborated on the origins of these histones and how they contribute to poor outcomes in patients.

“Histones are small positively charged proteins that bind to negatively charged DNA,” Dr. Abrams said. “Typically, they are found within the cell nucleus, where they are involved in the packaging of DNA. However, during cell death and cell damage, histones are released from the nucleus, extracellularly, and we find that they are very much elevated in critically ill patients that have undergone huge amounts of cell death and damage.”

Once in circulation, histones can make a bad situation even worse.

“Work by ourselves and others around the globe have found that when circulating histones are elevated in these critically ill patients, they’re extremely toxic,” Dr. Abrams said. “Histones can induce endothelial damage and vascular permeability.” In addition, he pointed out that histones are pro-inflammatory and pro-coagulant. “If you bring all of these phenomena together,” he pointed out, “histones induce organ injury and mortality in critically ill patients.”

“The current hypothesis is that if you’re treating patients with these antimalarials, and it’s killing off the parasite, it may cause the histones to be released, which is actually worse for certain patients,” Dr. Abrams explained.

Based on this hypothesis, the investigators developed an anti-histone therapy.

“We’ve got a small peptide that we use to bind to the histones that reduces their toxicity,” Dr. Abrams said. “If we coincubate the serum of [CM] patients with our anti-histone reagent and then put this onto a monolayer of endothelial cells, we see that this toxicity is inhibited. Therefore, this is suggestive that a major toxic factor within these patients are the extracellular histones.”

Providing additional support for the role of histones in cerebral toxicity, postmortem brain tissue from patients with CM showed localization of histones to the endothelium, which has been tied with increased permeability of vascular tissue. In addition, “we are seeing co-localization between the histones and the sequestration of the malarial parasite itself,” Dr. Abrams said. 

Concluding his presentation, he looked to the future.

“It’s difficult to get an animal model for malaria,” but he and his associates are currently working with other investigators to develop one. Once developed, the investigators plan on testing concurrent administration of anti-malarial therapy with antihistone therapy.

“What we’re hoping is that sometime in the future, maybe we’d be able to target circulating histones in this patient cohort to improve the survival of these patients,” Dr. Abrams said.

The investigators declared no conflicts of interest.

SOURCE: Moxon et al. BSH 2019. Abstract OR-034.

GLASGOW – Targeting circulating parasitic histones may hold promise for patients with cerebral malaria (CM), according to investigators.

A retrospective study, involving over 300 individuals, compared parasitic histone concentrations among patients with various forms of malaria and non-malarial illnesses, in addition to healthy controls, finding that elevated histone levels were associated with malarial disease severity and death, reported Simon Abrams, PhD, of the University of Liverpool, UK, a coauthor of the study. He noted that this research could guide the development of treatment strategies for hundreds of thousands of patients each year, particularly children.

“Cerebral malaria is the most severe form of Plasmodium falciparum infection, and despite effective anti-malarial therapy, between 10% and 20% of children that develop cerebral malaria die,” Dr. Abrams said during his presentation at the annual meeting of the British Society for Haematology. “This accounts for a huge amount of deaths per annum. Around 400,000 malarial deaths are in children in subSaharan Africa, and death typically occurs within 24 hours of hospital admission.”

In CM, the blood-brain barrier deteriorates, leading to brain swelling, hemorrhaging, clot formation, and in many cases, death, Dr. Abrams said. CM patients with the worst outcomes typically have retinal abnormalities on fundic exam, granting the disease subtype “retinopathy-positive.”

Aided by colleagues in Malawi, the investigators gathered over 300 patient samples for analysis. They found that patients with retinopathy-positive CM had higher mean extracellular histone levels than retinopathy-negative CM patients and healthy controls (22.6 mcg/ml, 6.31 mcg/ml, and 0.33 mcg/ml, respectively). In addition, retinopathy-positive CM patients who died had significantly higher levels of circulating histones, compared with similar patients who survived (35.7 mcg/ml vs. 21.6 mcg/ml).

These findings translated to predictive capability, as the investigators showed that patients with CM who had elevated histones when admitted to the hospital were at a higher risk of death than those with normal histone levels (P = .04). Unlike patients with CM, patients with uncomplicated malaria had relatively low histone levels (0.57 mcg/ml), as did patients with mild non-malarial febrile illness (1.73 mcg/ml) and non-malarial coma (1.73 mcg/ml).

During his presentation, Dr. Abrams elaborated on the origins of these histones and how they contribute to poor outcomes in patients.

“Histones are small positively charged proteins that bind to negatively charged DNA,” Dr. Abrams said. “Typically, they are found within the cell nucleus, where they are involved in the packaging of DNA. However, during cell death and cell damage, histones are released from the nucleus, extracellularly, and we find that they are very much elevated in critically ill patients that have undergone huge amounts of cell death and damage.”

Once in circulation, histones can make a bad situation even worse.

“Work by ourselves and others around the globe have found that when circulating histones are elevated in these critically ill patients, they’re extremely toxic,” Dr. Abrams said. “Histones can induce endothelial damage and vascular permeability.” In addition, he pointed out that histones are pro-inflammatory and pro-coagulant. “If you bring all of these phenomena together,” he pointed out, “histones induce organ injury and mortality in critically ill patients.”

“The current hypothesis is that if you’re treating patients with these antimalarials, and it’s killing off the parasite, it may cause the histones to be released, which is actually worse for certain patients,” Dr. Abrams explained.

Based on this hypothesis, the investigators developed an anti-histone therapy.

“We’ve got a small peptide that we use to bind to the histones that reduces their toxicity,” Dr. Abrams said. “If we coincubate the serum of [CM] patients with our anti-histone reagent and then put this onto a monolayer of endothelial cells, we see that this toxicity is inhibited. Therefore, this is suggestive that a major toxic factor within these patients are the extracellular histones.”

Providing additional support for the role of histones in cerebral toxicity, postmortem brain tissue from patients with CM showed localization of histones to the endothelium, which has been tied with increased permeability of vascular tissue. In addition, “we are seeing co-localization between the histones and the sequestration of the malarial parasite itself,” Dr. Abrams said. 

Concluding his presentation, he looked to the future.

“It’s difficult to get an animal model for malaria,” but he and his associates are currently working with other investigators to develop one. Once developed, the investigators plan on testing concurrent administration of anti-malarial therapy with antihistone therapy.

“What we’re hoping is that sometime in the future, maybe we’d be able to target circulating histones in this patient cohort to improve the survival of these patients,” Dr. Abrams said.

The investigators declared no conflicts of interest.

SOURCE: Moxon et al. BSH 2019. Abstract OR-034.

GLASGOW – Targeting circulating parasitic histones may hold promise for patients with cerebral malaria (CM), according to investigators.

A retrospective study, involving over 300 individuals, compared parasitic histone concentrations among patients with various forms of malaria and non-malarial illnesses, in addition to healthy controls, finding that elevated histone levels were associated with malarial disease severity and death, reported Simon Abrams, PhD, of the University of Liverpool, UK, a coauthor of the study. He noted that this research could guide the development of treatment strategies for hundreds of thousands of patients each year, particularly children.

“Cerebral malaria is the most severe form of Plasmodium falciparum infection, and despite effective anti-malarial therapy, between 10% and 20% of children that develop cerebral malaria die,” Dr. Abrams said during his presentation at the annual meeting of the British Society for Haematology. “This accounts for a huge amount of deaths per annum. Around 400,000 malarial deaths are in children in subSaharan Africa, and death typically occurs within 24 hours of hospital admission.”

In CM, the blood-brain barrier deteriorates, leading to brain swelling, hemorrhaging, clot formation, and in many cases, death, Dr. Abrams said. CM patients with the worst outcomes typically have retinal abnormalities on fundic exam, granting the disease subtype “retinopathy-positive.”

Aided by colleagues in Malawi, the investigators gathered over 300 patient samples for analysis. They found that patients with retinopathy-positive CM had higher mean extracellular histone levels than retinopathy-negative CM patients and healthy controls (22.6 mcg/ml, 6.31 mcg/ml, and 0.33 mcg/ml, respectively). In addition, retinopathy-positive CM patients who died had significantly higher levels of circulating histones, compared with similar patients who survived (35.7 mcg/ml vs. 21.6 mcg/ml).

These findings translated to predictive capability, as the investigators showed that patients with CM who had elevated histones when admitted to the hospital were at a higher risk of death than those with normal histone levels (P = .04). Unlike patients with CM, patients with uncomplicated malaria had relatively low histone levels (0.57 mcg/ml), as did patients with mild non-malarial febrile illness (1.73 mcg/ml) and non-malarial coma (1.73 mcg/ml).

During his presentation, Dr. Abrams elaborated on the origins of these histones and how they contribute to poor outcomes in patients.

“Histones are small positively charged proteins that bind to negatively charged DNA,” Dr. Abrams said. “Typically, they are found within the cell nucleus, where they are involved in the packaging of DNA. However, during cell death and cell damage, histones are released from the nucleus, extracellularly, and we find that they are very much elevated in critically ill patients that have undergone huge amounts of cell death and damage.”

Once in circulation, histones can make a bad situation even worse.

“Work by ourselves and others around the globe have found that when circulating histones are elevated in these critically ill patients, they’re extremely toxic,” Dr. Abrams said. “Histones can induce endothelial damage and vascular permeability.” In addition, he pointed out that histones are pro-inflammatory and pro-coagulant. “If you bring all of these phenomena together,” he pointed out, “histones induce organ injury and mortality in critically ill patients.”

“The current hypothesis is that if you’re treating patients with these antimalarials, and it’s killing off the parasite, it may cause the histones to be released, which is actually worse for certain patients,” Dr. Abrams explained.

Based on this hypothesis, the investigators developed an anti-histone therapy.

“We’ve got a small peptide that we use to bind to the histones that reduces their toxicity,” Dr. Abrams said. “If we coincubate the serum of [CM] patients with our anti-histone reagent and then put this onto a monolayer of endothelial cells, we see that this toxicity is inhibited. Therefore, this is suggestive that a major toxic factor within these patients are the extracellular histones.”

Providing additional support for the role of histones in cerebral toxicity, postmortem brain tissue from patients with CM showed localization of histones to the endothelium, which has been tied with increased permeability of vascular tissue. In addition, “we are seeing co-localization between the histones and the sequestration of the malarial parasite itself,” Dr. Abrams said. 

Concluding his presentation, he looked to the future.

“It’s difficult to get an animal model for malaria,” but he and his associates are currently working with other investigators to develop one. Once developed, the investigators plan on testing concurrent administration of anti-malarial therapy with antihistone therapy.

“What we’re hoping is that sometime in the future, maybe we’d be able to target circulating histones in this patient cohort to improve the survival of these patients,” Dr. Abrams said.

The investigators declared no conflicts of interest.

SOURCE: Moxon et al. BSH 2019. Abstract OR-034.

Nasal high-frequency oscillatory ventilation (NHFOV) surpassed nasal continuous positive airway pressure (NCPAP) at reducing the risk of reintubation among preterm infants, in a randomized trial of 206 preterm infants with respiratory failure.

Previous studies have supported the use of NHFOV as more effective for reducing CO2 and for lowering the risk of reintubation compared with NCPAP. But no randomized, controlled trials had compared the outcomes for preterm infants in particular, wrote Long Chen, MD, PhD, of Children’s Hospital of Chongqing Medical University, Chongqing, China, and colleagues.

Their study, published in Chest, was conducted at a single tertiary NICU in China between May 2017 and May 2018, and randomized infants with a gestational age less than 37 weeks to NHFOV (103 infants) or NCPAP (103 infants). Infants with major congenital abnormalities were excluded. The infants included 127 (61.7%) diagnosed with respiratory distress syndrome (RDS), 53 (25.7%) diagnosed with acute RDS (ARDS), and 26 (12.6%) diagnosed with both RDS and ARDS.

Overall, the reintubation rate within 6 hours was significantly lower among infants treated with NHFOV compared with those treated with NCPAP (15.5% vs. 34%, P = .002), and in the subset of infants with ARDS (23.5% vs. 52.6%, P = .032). Among infants with a gestational age of 32 weeks or less, reintuibation rates were also significantly lower among those treated with NHFOV (26.1% vs. 55.6%, P = .004).


In addition, PCO2 levels, 6 hours after extubation, were significantly lower among infants on NHFOV, compared with those on NCPAP (49.6 vs. 56.9 P = .00). The hospital stay, a secondary outcome, was significantly shorter among the infants treated with NHFOV, than those treated with NCPAP (22 days, vs. 27.6 days, P =.011).

Although the researchers observed some nasal trauma in NHFOV-treated patients, and intestinal dilation in both groups similar to side effects seen in previous studies, no feeding intolerance or skin lesions were associated with NHFOV. The study findings were consistent with those from previous studies, and suggested that the causes of respiratory failure might account for the differences between the treatment groups, they noted.

“RDS is primarily restrictive in the acute phase, and the high frequency oscillation over CPAP does not therefore bring any benefit. However, ARDS is both restrictive and obstructive in the acute phase due to the nature of ARDS,” and NHFOV is “able to improve oxygenation,” they added.

The study findings were limited by several factors including the use of data from a single center and the small number of infants younger than 28 weeks’ gestation, the researchers noted. However, they added, two international, multicenter, randomized controlled trials are in the works.

The study was supported by Social Livelihood Program of 38 Chongqing Science and Technology Commission, China. The researchers had no financial conflicts to disclose.

SOURCE: Long C et al. Chest. 2019; 155(4): 740-8.

Nasal high-frequency oscillatory ventilation (NHFOV) surpassed nasal continuous positive airway pressure (NCPAP) at reducing the risk of reintubation among preterm infants, in a randomized trial of 206 preterm infants with respiratory failure.

Previous studies have supported the use of NHFOV as more effective for reducing CO2 and for lowering the risk of reintubation compared with NCPAP. But no randomized, controlled trials had compared the outcomes for preterm infants in particular, wrote Long Chen, MD, PhD, of Children’s Hospital of Chongqing Medical University, Chongqing, China, and colleagues.

Their study, published in Chest, was conducted at a single tertiary NICU in China between May 2017 and May 2018, and randomized infants with a gestational age less than 37 weeks to NHFOV (103 infants) or NCPAP (103 infants). Infants with major congenital abnormalities were excluded. The infants included 127 (61.7%) diagnosed with respiratory distress syndrome (RDS), 53 (25.7%) diagnosed with acute RDS (ARDS), and 26 (12.6%) diagnosed with both RDS and ARDS.

Overall, the reintubation rate within 6 hours was significantly lower among infants treated with NHFOV compared with those treated with NCPAP (15.5% vs. 34%, P = .002), and in the subset of infants with ARDS (23.5% vs. 52.6%, P = .032). Among infants with a gestational age of 32 weeks or less, reintuibation rates were also significantly lower among those treated with NHFOV (26.1% vs. 55.6%, P = .004).


In addition, PCO2 levels, 6 hours after extubation, were significantly lower among infants on NHFOV, compared with those on NCPAP (49.6 vs. 56.9 P = .00). The hospital stay, a secondary outcome, was significantly shorter among the infants treated with NHFOV, than those treated with NCPAP (22 days, vs. 27.6 days, P =.011).

Although the researchers observed some nasal trauma in NHFOV-treated patients, and intestinal dilation in both groups similar to side effects seen in previous studies, no feeding intolerance or skin lesions were associated with NHFOV. The study findings were consistent with those from previous studies, and suggested that the causes of respiratory failure might account for the differences between the treatment groups, they noted.

“RDS is primarily restrictive in the acute phase, and the high frequency oscillation over CPAP does not therefore bring any benefit. However, ARDS is both restrictive and obstructive in the acute phase due to the nature of ARDS,” and NHFOV is “able to improve oxygenation,” they added.

The study findings were limited by several factors including the use of data from a single center and the small number of infants younger than 28 weeks’ gestation, the researchers noted. However, they added, two international, multicenter, randomized controlled trials are in the works.

The study was supported by Social Livelihood Program of 38 Chongqing Science and Technology Commission, China. The researchers had no financial conflicts to disclose.

SOURCE: Long C et al. Chest. 2019; 155(4): 740-8.

Nasal high-frequency oscillatory ventilation (NHFOV) surpassed nasal continuous positive airway pressure (NCPAP) at reducing the risk of reintubation among preterm infants, in a randomized trial of 206 preterm infants with respiratory failure.

Previous studies have supported the use of NHFOV as more effective for reducing CO2 and for lowering the risk of reintubation compared with NCPAP. But no randomized, controlled trials had compared the outcomes for preterm infants in particular, wrote Long Chen, MD, PhD, of Children’s Hospital of Chongqing Medical University, Chongqing, China, and colleagues.

Their study, published in Chest, was conducted at a single tertiary NICU in China between May 2017 and May 2018, and randomized infants with a gestational age less than 37 weeks to NHFOV (103 infants) or NCPAP (103 infants). Infants with major congenital abnormalities were excluded. The infants included 127 (61.7%) diagnosed with respiratory distress syndrome (RDS), 53 (25.7%) diagnosed with acute RDS (ARDS), and 26 (12.6%) diagnosed with both RDS and ARDS.

Overall, the reintubation rate within 6 hours was significantly lower among infants treated with NHFOV compared with those treated with NCPAP (15.5% vs. 34%, P = .002), and in the subset of infants with ARDS (23.5% vs. 52.6%, P = .032). Among infants with a gestational age of 32 weeks or less, reintuibation rates were also significantly lower among those treated with NHFOV (26.1% vs. 55.6%, P = .004).


In addition, PCO2 levels, 6 hours after extubation, were significantly lower among infants on NHFOV, compared with those on NCPAP (49.6 vs. 56.9 P = .00). The hospital stay, a secondary outcome, was significantly shorter among the infants treated with NHFOV, than those treated with NCPAP (22 days, vs. 27.6 days, P =.011).

Although the researchers observed some nasal trauma in NHFOV-treated patients, and intestinal dilation in both groups similar to side effects seen in previous studies, no feeding intolerance or skin lesions were associated with NHFOV. The study findings were consistent with those from previous studies, and suggested that the causes of respiratory failure might account for the differences between the treatment groups, they noted.

“RDS is primarily restrictive in the acute phase, and the high frequency oscillation over CPAP does not therefore bring any benefit. However, ARDS is both restrictive and obstructive in the acute phase due to the nature of ARDS,” and NHFOV is “able to improve oxygenation,” they added.

The study findings were limited by several factors including the use of data from a single center and the small number of infants younger than 28 weeks’ gestation, the researchers noted. However, they added, two international, multicenter, randomized controlled trials are in the works.

The study was supported by Social Livelihood Program of 38 Chongqing Science and Technology Commission, China. The researchers had no financial conflicts to disclose.

SOURCE: Long C et al. Chest. 2019; 155(4): 740-8.

DENVER – A survey from a dermatology practice in Houston found that among patients seeking corrective treatment for laser tattoo removal, 79% had complications from previous removal attempts and 63% were treated in non-clinic facilities by a non-physician provider without physician supervision.

The findings come from a single-center study that sought to identify the type, burden, and frequency of complications from laser tattoo removal, a procedure offered by both physician and non-physician facilities. “Laser tattoo removal is increasing in popularity,” lead study author Amanda K. Suggs, MD, said at the annual conference of the American Society for Laser Medicine and Surgery.

Dr. Suggs and Paul M. Friedman, MD, of Houston-based Dermatology and Laser Surgery, have observed an increase in patients seeking corrective tattoo removal after complications from and lack of efficacy of prior treatments provided predominantly at non-clinic facilities, including medical spas and tattoo removal clinics –so they decided to interview 19 patients who presented to their practice seeking corrective laser tattoo removal. The majority (84%) were female, their mean age was 34 years old, and 53% had Fitzpatrick skin types IV or higher. Nearly three-quarters of tattoos (74%) consisted of multiple colors, which are known to be more difficult to treat. Of the patients seeking corrective treatment, 42% were seeking removal of more than one tattoo.

Prior to coming to their office, the patients had undergone an average of seven prior tattoo removal treatments and 72% of patients were treated by a non-physician provider at some point. Nearly two-thirds of patients (63%) were treated in non-clinic facilities. “All patients were unsatisfied with the degree of improvement, and 79% had at least one complication from their prior treatments,” said Dr. Suggs, who is a fellow at the practice.

Of the 15 patients with prior treatment complications, 64% were treated by a non-physician provider. The most common complication was scarring (53%), followed by dyspigmentation (47%), blistering (20%) and paradoxical darkening (20%). Six patients (40%) had more than one complication. Patients with Fitzpatrick skin types IV or higher had a higher proportion of scarring and dyspigmentation (63% and 71%, respectively) compared with those with other skin types. “This suggests that we should use caution when treating tattoos in patients with higher Fitzpatrick skin types, and use appropriate settings and endpoints when treating these patients,” Dr. Suggs said.


When she and Dr. Friedman interviewed the patients about their prior treatment experience elsewhere, all said they experienced excessive pain, only 33% received topical anesthesia, and none reported receiving an injectable anesthesia.

At the Dermatology and Laser Surgery Center, the protocol for corrective laser tattoo removal involves injectable anesthesia, Dr. Suggs said. They use a picosecond laser, a perfluorodecalin patch, and, if needed, nonablative fractional resurfacing at 1550 nm for scarring. The wavelength used for the picosecond laser (1064nm, 785nm or 532nm) is chosen based on patient characteristics and tattoo color or colors.

Lance Sitton Photography/Thinkstock

In a subset analysis, the investigators interviewed eight patients again after undergoing laser tattoo removal at their practice. All underwent treatment with a picosecond laser, perfluorodecalin patch, and injectable anesthesia. All reported minimal to no pain during the procedure and an optimal experience. No complications were noted.

Dr. Friedman and Dr. Suggs emphasized that consumers should be aware of the risks and potential for complications from laser tattoo removal. They recommend that all consumers – especially those at higher risk for complications such as higher Fitzpatrick skin type patients and those with multicolored tattoos – choose a provider with extensive training in the procedure, such as a board-certified dermatologist or plastic surgeon.

Dr. Suggs disclosed that she is an ambassador for Tri Sirena sun protective athletic apparel. Dr. Friedman disclosed that he is a member of the advisory board for Allergan, Solta Medical, Syneron-Candela, and Sienna Biopharmaceuticals. He is also a research investigator for Syneron-Candela and has received a research grant from Sienna.

[email protected]

DENVER – A survey from a dermatology practice in Houston found that among patients seeking corrective treatment for laser tattoo removal, 79% had complications from previous removal attempts and 63% were treated in non-clinic facilities by a non-physician provider without physician supervision.

The findings come from a single-center study that sought to identify the type, burden, and frequency of complications from laser tattoo removal, a procedure offered by both physician and non-physician facilities. “Laser tattoo removal is increasing in popularity,” lead study author Amanda K. Suggs, MD, said at the annual conference of the American Society for Laser Medicine and Surgery.

Dr. Suggs and Paul M. Friedman, MD, of Houston-based Dermatology and Laser Surgery, have observed an increase in patients seeking corrective tattoo removal after complications from and lack of efficacy of prior treatments provided predominantly at non-clinic facilities, including medical spas and tattoo removal clinics –so they decided to interview 19 patients who presented to their practice seeking corrective laser tattoo removal. The majority (84%) were female, their mean age was 34 years old, and 53% had Fitzpatrick skin types IV or higher. Nearly three-quarters of tattoos (74%) consisted of multiple colors, which are known to be more difficult to treat. Of the patients seeking corrective treatment, 42% were seeking removal of more than one tattoo.

Prior to coming to their office, the patients had undergone an average of seven prior tattoo removal treatments and 72% of patients were treated by a non-physician provider at some point. Nearly two-thirds of patients (63%) were treated in non-clinic facilities. “All patients were unsatisfied with the degree of improvement, and 79% had at least one complication from their prior treatments,” said Dr. Suggs, who is a fellow at the practice.

Of the 15 patients with prior treatment complications, 64% were treated by a non-physician provider. The most common complication was scarring (53%), followed by dyspigmentation (47%), blistering (20%) and paradoxical darkening (20%). Six patients (40%) had more than one complication. Patients with Fitzpatrick skin types IV or higher had a higher proportion of scarring and dyspigmentation (63% and 71%, respectively) compared with those with other skin types. “This suggests that we should use caution when treating tattoos in patients with higher Fitzpatrick skin types, and use appropriate settings and endpoints when treating these patients,” Dr. Suggs said.


When she and Dr. Friedman interviewed the patients about their prior treatment experience elsewhere, all said they experienced excessive pain, only 33% received topical anesthesia, and none reported receiving an injectable anesthesia.

At the Dermatology and Laser Surgery Center, the protocol for corrective laser tattoo removal involves injectable anesthesia, Dr. Suggs said. They use a picosecond laser, a perfluorodecalin patch, and, if needed, nonablative fractional resurfacing at 1550 nm for scarring. The wavelength used for the picosecond laser (1064nm, 785nm or 532nm) is chosen based on patient characteristics and tattoo color or colors.

Lance Sitton Photography/Thinkstock

In a subset analysis, the investigators interviewed eight patients again after undergoing laser tattoo removal at their practice. All underwent treatment with a picosecond laser, perfluorodecalin patch, and injectable anesthesia. All reported minimal to no pain during the procedure and an optimal experience. No complications were noted.

Dr. Friedman and Dr. Suggs emphasized that consumers should be aware of the risks and potential for complications from laser tattoo removal. They recommend that all consumers – especially those at higher risk for complications such as higher Fitzpatrick skin type patients and those with multicolored tattoos – choose a provider with extensive training in the procedure, such as a board-certified dermatologist or plastic surgeon.

Dr. Suggs disclosed that she is an ambassador for Tri Sirena sun protective athletic apparel. Dr. Friedman disclosed that he is a member of the advisory board for Allergan, Solta Medical, Syneron-Candela, and Sienna Biopharmaceuticals. He is also a research investigator for Syneron-Candela and has received a research grant from Sienna.

[email protected]

DENVER – A survey from a dermatology practice in Houston found that among patients seeking corrective treatment for laser tattoo removal, 79% had complications from previous removal attempts and 63% were treated in non-clinic facilities by a non-physician provider without physician supervision.

The findings come from a single-center study that sought to identify the type, burden, and frequency of complications from laser tattoo removal, a procedure offered by both physician and non-physician facilities. “Laser tattoo removal is increasing in popularity,” lead study author Amanda K. Suggs, MD, said at the annual conference of the American Society for Laser Medicine and Surgery.

Dr. Suggs and Paul M. Friedman, MD, of Houston-based Dermatology and Laser Surgery, have observed an increase in patients seeking corrective tattoo removal after complications from and lack of efficacy of prior treatments provided predominantly at non-clinic facilities, including medical spas and tattoo removal clinics –so they decided to interview 19 patients who presented to their practice seeking corrective laser tattoo removal. The majority (84%) were female, their mean age was 34 years old, and 53% had Fitzpatrick skin types IV or higher. Nearly three-quarters of tattoos (74%) consisted of multiple colors, which are known to be more difficult to treat. Of the patients seeking corrective treatment, 42% were seeking removal of more than one tattoo.

Prior to coming to their office, the patients had undergone an average of seven prior tattoo removal treatments and 72% of patients were treated by a non-physician provider at some point. Nearly two-thirds of patients (63%) were treated in non-clinic facilities. “All patients were unsatisfied with the degree of improvement, and 79% had at least one complication from their prior treatments,” said Dr. Suggs, who is a fellow at the practice.

Of the 15 patients with prior treatment complications, 64% were treated by a non-physician provider. The most common complication was scarring (53%), followed by dyspigmentation (47%), blistering (20%) and paradoxical darkening (20%). Six patients (40%) had more than one complication. Patients with Fitzpatrick skin types IV or higher had a higher proportion of scarring and dyspigmentation (63% and 71%, respectively) compared with those with other skin types. “This suggests that we should use caution when treating tattoos in patients with higher Fitzpatrick skin types, and use appropriate settings and endpoints when treating these patients,” Dr. Suggs said.


When she and Dr. Friedman interviewed the patients about their prior treatment experience elsewhere, all said they experienced excessive pain, only 33% received topical anesthesia, and none reported receiving an injectable anesthesia.

At the Dermatology and Laser Surgery Center, the protocol for corrective laser tattoo removal involves injectable anesthesia, Dr. Suggs said. They use a picosecond laser, a perfluorodecalin patch, and, if needed, nonablative fractional resurfacing at 1550 nm for scarring. The wavelength used for the picosecond laser (1064nm, 785nm or 532nm) is chosen based on patient characteristics and tattoo color or colors.

Lance Sitton Photography/Thinkstock

In a subset analysis, the investigators interviewed eight patients again after undergoing laser tattoo removal at their practice. All underwent treatment with a picosecond laser, perfluorodecalin patch, and injectable anesthesia. All reported minimal to no pain during the procedure and an optimal experience. No complications were noted.

Dr. Friedman and Dr. Suggs emphasized that consumers should be aware of the risks and potential for complications from laser tattoo removal. They recommend that all consumers – especially those at higher risk for complications such as higher Fitzpatrick skin type patients and those with multicolored tattoos – choose a provider with extensive training in the procedure, such as a board-certified dermatologist or plastic surgeon.

Dr. Suggs disclosed that she is an ambassador for Tri Sirena sun protective athletic apparel. Dr. Friedman disclosed that he is a member of the advisory board for Allergan, Solta Medical, Syneron-Candela, and Sienna Biopharmaceuticals. He is also a research investigator for Syneron-Candela and has received a research grant from Sienna.

[email protected]

MILWAUKEE – A new study of children with sickle cell disease found prevalent opioid use, with one in five preschoolers having had an opioid prescribed and filled for them.

Kari Oakes/MDedge News

The Medicaid claims database analysis looked at a one-year snapshot of prescriptions filled for a variety of opioids among children and young adults in North Carolina, said Nancy Crego, PhD, in an interview at a poster session of the scientific meeting of the American Pain Society.

Dr. Crego and her colleagues at Duke University School of Nursing, Durham, N.C., studied 1,560 children and young adults aged 0-22 years with sickle cell disease who received Medicaid; in all, 586 (38%) had an opioid prescription filled during the year-long study period.

Among adolescents and young adults with sickle cell disease, outpatient opioid prescriptions were common, with increasing prescription fills seen through the middle years and young adulthood. “Opioid prescription claims were prevalent across all age groups,” wrote Dr. Crego and her associates.

Though 20% of preschoolers (87 of 428) had had a prescription filled for opioids, the rates of opioid prescribing increased with age. Of adolescents aged 15-18 years, 54% (154 of 284) had filled an opioid prescription, as had 50% (110 of 221) of those aged 19-22 years.

For the 366 school-aged children aged 6-10 years, 117 (32%) had an opioid prescription filled. The number of prescriptions filled per patient on an annual basis for this age group ranged from one to 10.


There was a wide variation in the number of prescriptions filled in all other age groups over the study period as well. For school-aged children, the range was 1 to 10, and 1 to 18 for middle schoolers aged 11-14 years. Adolescents filled from 1-30 prescriptions, and for young adults, the range was 1-24.

Though the rates of opioid prescribing increased with age, the number of doses per prescription actually fell throughout the adolescent and young adult years. In an interview at the poster presentation, Dr. Crego speculated that this decrease observed with increasing age might reflect provider concern about opioid misuse and diversion, though the study methodology didn’t allow them to examine this.

Dr. Crego said that she was surprised by the high numbers of children who were receiving opioid prescriptions in the preschool years. “I wonder what their parents are being taught about how to administer these medications” to this very young age group, she commented.

Opioids included in the claims database analysis included morphine, hydromorphone, hydrocodone, oxycodone, oxymorphone, methadone, fentanyl, codeine, and tramadol.

Children with sickle cell disease are exposed to opioids in early childhood,” Dr. Crego and her colleagues wrote in the poster, but they acknowledged that “it is unknown if this early exposure increases the risk of opioid misuse later in life in this population ... Prescribers should incorporate continuous assessments for potential misuse and abuse in all age groups.”

“Most of the data that we have on opioid prescription claims in children usually exclude chronically ill children; they’re almost all of acutely ill children, and quite a bit of it is on postoperative care,” Dr. Crego said. The current study captures early-life prescribing “for somebody who’s going to be on opioids for a lot of their life,” she noted.

The studies of opioids used for acute pain, she said, showed that parents would often “administer opioids for inappropriate indications.” She is now conducting a qualitative study investigating pharmacologic and non-pharmacologic pain interventions for children with sickle cell disease. She’s also investigating how parents decide to administer opioids: “What did they see in their child that would prompt them to give an opioid versus giving another type of analgesic?”

There are some limitations to working with a claims database, acknowledged Dr. Crego: “We don’t know about their actual use, because we don’t know how often they are taking it, but we know it’s a filled opioid prescription.”

Dr. Crego said that more work is needed to examine how parents administer opioids to their children with sickle cell disease, and to learn more about what parents are told – and what they understand – about how their child’s pain should be managed. Also, she added, more research is needed on non-pharmacologic pain management for pediatric patients with sickle cell disease.

The study was funded by the Agency for Healthcare Research and Quality. Dr. Crego and her coauthors reported no conflicts of interest.

[email protected]

SOURCE: Crego, N. et al. APS 2019.

MILWAUKEE – A new study of children with sickle cell disease found prevalent opioid use, with one in five preschoolers having had an opioid prescribed and filled for them.

Kari Oakes/MDedge News

The Medicaid claims database analysis looked at a one-year snapshot of prescriptions filled for a variety of opioids among children and young adults in North Carolina, said Nancy Crego, PhD, in an interview at a poster session of the scientific meeting of the American Pain Society.

Dr. Crego and her colleagues at Duke University School of Nursing, Durham, N.C., studied 1,560 children and young adults aged 0-22 years with sickle cell disease who received Medicaid; in all, 586 (38%) had an opioid prescription filled during the year-long study period.

Among adolescents and young adults with sickle cell disease, outpatient opioid prescriptions were common, with increasing prescription fills seen through the middle years and young adulthood. “Opioid prescription claims were prevalent across all age groups,” wrote Dr. Crego and her associates.

Though 20% of preschoolers (87 of 428) had had a prescription filled for opioids, the rates of opioid prescribing increased with age. Of adolescents aged 15-18 years, 54% (154 of 284) had filled an opioid prescription, as had 50% (110 of 221) of those aged 19-22 years.

For the 366 school-aged children aged 6-10 years, 117 (32%) had an opioid prescription filled. The number of prescriptions filled per patient on an annual basis for this age group ranged from one to 10.


There was a wide variation in the number of prescriptions filled in all other age groups over the study period as well. For school-aged children, the range was 1 to 10, and 1 to 18 for middle schoolers aged 11-14 years. Adolescents filled from 1-30 prescriptions, and for young adults, the range was 1-24.

Though the rates of opioid prescribing increased with age, the number of doses per prescription actually fell throughout the adolescent and young adult years. In an interview at the poster presentation, Dr. Crego speculated that this decrease observed with increasing age might reflect provider concern about opioid misuse and diversion, though the study methodology didn’t allow them to examine this.

Dr. Crego said that she was surprised by the high numbers of children who were receiving opioid prescriptions in the preschool years. “I wonder what their parents are being taught about how to administer these medications” to this very young age group, she commented.

Opioids included in the claims database analysis included morphine, hydromorphone, hydrocodone, oxycodone, oxymorphone, methadone, fentanyl, codeine, and tramadol.

Children with sickle cell disease are exposed to opioids in early childhood,” Dr. Crego and her colleagues wrote in the poster, but they acknowledged that “it is unknown if this early exposure increases the risk of opioid misuse later in life in this population ... Prescribers should incorporate continuous assessments for potential misuse and abuse in all age groups.”

“Most of the data that we have on opioid prescription claims in children usually exclude chronically ill children; they’re almost all of acutely ill children, and quite a bit of it is on postoperative care,” Dr. Crego said. The current study captures early-life prescribing “for somebody who’s going to be on opioids for a lot of their life,” she noted.

The studies of opioids used for acute pain, she said, showed that parents would often “administer opioids for inappropriate indications.” She is now conducting a qualitative study investigating pharmacologic and non-pharmacologic pain interventions for children with sickle cell disease. She’s also investigating how parents decide to administer opioids: “What did they see in their child that would prompt them to give an opioid versus giving another type of analgesic?”

There are some limitations to working with a claims database, acknowledged Dr. Crego: “We don’t know about their actual use, because we don’t know how often they are taking it, but we know it’s a filled opioid prescription.”

Dr. Crego said that more work is needed to examine how parents administer opioids to their children with sickle cell disease, and to learn more about what parents are told – and what they understand – about how their child’s pain should be managed. Also, she added, more research is needed on non-pharmacologic pain management for pediatric patients with sickle cell disease.

The study was funded by the Agency for Healthcare Research and Quality. Dr. Crego and her coauthors reported no conflicts of interest.

[email protected]

SOURCE: Crego, N. et al. APS 2019.

MILWAUKEE – A new study of children with sickle cell disease found prevalent opioid use, with one in five preschoolers having had an opioid prescribed and filled for them.

Kari Oakes/MDedge News

The Medicaid claims database analysis looked at a one-year snapshot of prescriptions filled for a variety of opioids among children and young adults in North Carolina, said Nancy Crego, PhD, in an interview at a poster session of the scientific meeting of the American Pain Society.

Dr. Crego and her colleagues at Duke University School of Nursing, Durham, N.C., studied 1,560 children and young adults aged 0-22 years with sickle cell disease who received Medicaid; in all, 586 (38%) had an opioid prescription filled during the year-long study period.

Among adolescents and young adults with sickle cell disease, outpatient opioid prescriptions were common, with increasing prescription fills seen through the middle years and young adulthood. “Opioid prescription claims were prevalent across all age groups,” wrote Dr. Crego and her associates.

Though 20% of preschoolers (87 of 428) had had a prescription filled for opioids, the rates of opioid prescribing increased with age. Of adolescents aged 15-18 years, 54% (154 of 284) had filled an opioid prescription, as had 50% (110 of 221) of those aged 19-22 years.

For the 366 school-aged children aged 6-10 years, 117 (32%) had an opioid prescription filled. The number of prescriptions filled per patient on an annual basis for this age group ranged from one to 10.


There was a wide variation in the number of prescriptions filled in all other age groups over the study period as well. For school-aged children, the range was 1 to 10, and 1 to 18 for middle schoolers aged 11-14 years. Adolescents filled from 1-30 prescriptions, and for young adults, the range was 1-24.

Though the rates of opioid prescribing increased with age, the number of doses per prescription actually fell throughout the adolescent and young adult years. In an interview at the poster presentation, Dr. Crego speculated that this decrease observed with increasing age might reflect provider concern about opioid misuse and diversion, though the study methodology didn’t allow them to examine this.

Dr. Crego said that she was surprised by the high numbers of children who were receiving opioid prescriptions in the preschool years. “I wonder what their parents are being taught about how to administer these medications” to this very young age group, she commented.

Opioids included in the claims database analysis included morphine, hydromorphone, hydrocodone, oxycodone, oxymorphone, methadone, fentanyl, codeine, and tramadol.

Children with sickle cell disease are exposed to opioids in early childhood,” Dr. Crego and her colleagues wrote in the poster, but they acknowledged that “it is unknown if this early exposure increases the risk of opioid misuse later in life in this population ... Prescribers should incorporate continuous assessments for potential misuse and abuse in all age groups.”

“Most of the data that we have on opioid prescription claims in children usually exclude chronically ill children; they’re almost all of acutely ill children, and quite a bit of it is on postoperative care,” Dr. Crego said. The current study captures early-life prescribing “for somebody who’s going to be on opioids for a lot of their life,” she noted.

The studies of opioids used for acute pain, she said, showed that parents would often “administer opioids for inappropriate indications.” She is now conducting a qualitative study investigating pharmacologic and non-pharmacologic pain interventions for children with sickle cell disease. She’s also investigating how parents decide to administer opioids: “What did they see in their child that would prompt them to give an opioid versus giving another type of analgesic?”

There are some limitations to working with a claims database, acknowledged Dr. Crego: “We don’t know about their actual use, because we don’t know how often they are taking it, but we know it’s a filled opioid prescription.”

Dr. Crego said that more work is needed to examine how parents administer opioids to their children with sickle cell disease, and to learn more about what parents are told – and what they understand – about how their child’s pain should be managed. Also, she added, more research is needed on non-pharmacologic pain management for pediatric patients with sickle cell disease.

The study was funded by the Agency for Healthcare Research and Quality. Dr. Crego and her coauthors reported no conflicts of interest.

[email protected]

SOURCE: Crego, N. et al. APS 2019.

MILWAUKEE – A stepped-care approach to youth with functional abdominal pain disorders may be effective in targeting those with comorbid anxiety, according to ongoing research.

A study of 79 pediatric patients with a functional abdominal pain disorder (FAPD) and co-occurring anxiety found that those who received cognitive behavioral therapy (CBT) that included a component to address anxiety had less functional disability and anxiety than those who received treatment as usual. Pain scores also dropped, though the difference was not statistically significant.

The patients, aged 9-14 years and mostly white and female, were randomized to treatment allocation. Functional disability scores were significantly lower post-treatment for those who received the stepped therapy compared with the treatment as usual group (P less than .05, Cohen’s D = .49). This indicates a moderate effect size, said Natoshia Cunningham, PhD, speaking at the scientific meeting of the American Pain Society.

Mean scores on an anxiety rating scale also dropped below the threshold for clinical anxiety for those receiving the stepped therapy; on average, the treatment as usual group still scored above the clinical anxiety threshold after treatment (P for difference = .05).

The study, part of ongoing research, tests a hybrid online intervention, dubbed Aim to Decrease Anxiety and Pain Treatment, or ADAPT. The ADAPT program includes some common elements of CBT for anxiety that were not previously included in the pediatric pain CBT in use for the FAPD patients, she said.


The hybrid program began with two in-person sessions, each lasting one hour. These were followed by up to four web-based sessions. Patients viewed videos, read some material online, and complete activities with follow-up assessments. The web-based component was structured so that providers can see how patients fare on assessments – and even see which activities had been opened or completed. This, said Dr. Cunningham, allowed the treating provider to tailor what’s addressed in the associated weekly phone checks that accompany the online content.

Parents were also given practical, evidence-based advice to help manage their child’s FAPD. These include encouraging children to be independent in pain management, stopping “status checks,” encouraging normal school and social activities, and avoiding special privileges when pain interferes with activities.

Overall, up to 40% of pediatric functional abdominal pain patients may not respond to CBT, the most efficacious treatment known, said Dr. Cunningham, a pediatric psychologist at the University of Cincinnati. Her research indicates that comorbid anxiety may predict poor response, and that addressing anxiety improves pain and disability in this complex, common disorder.

With a brief psychosocial screening that identifies patients with anxiety, Dr. Cunningham and her colleagues can implement the targeted, partially web-based therapy strategy that tackles anxiety along with CBT for functional abdominal pain.

“Anxiety is common and related to poor outcomes,” noted Dr. Cunningham, She added that overall, half or more of individuals with chronic pain also have anxiety. Among children with FAPD, “Clinical anxiety predicts disability and poor treatment response.”

The first step, she said, was identifying the patients with FAPD who had anxiety, including those with subclinical anxiety.

At intake, children coming to the Cincinnati Children’s Hospital’s gastroenterology clinic complete anxiety screening via the Screen for Child Anxiety Related Emotional Disorders (SCARED) (Depress Anxiety. 2000;12[2]:85-91). Disability and pain are assessed by the Functional Disability Inventory and the Numeric Rating Scale (J Pediatr Psychol. 1991 Feb;16[1]:39-58).

In earlier research, Dr. Cunningham and her collaborators found a significant association between anxiety and both higher pain levels and more disability. And, clinically significant anxiety was more likely among the FAPD patients with persistent disability after six months of treatment.

A surprising finding from the screenings, said Dr. Cunningham, is that youth endorsed more anxiety symptoms in self-assessment than their parents observed. “Children are often their own best informants of their internalizing symptoms,” she said. “Not only do their parents not notice it, it may not be obvious to their providers, either.”

Since many children with FAPD have anxiety, the next question was “How do we better enhance their treatments?” she continued. To answer that question, she took one step back: “How do these youth respond to our current best practice?”

Looking at Cincinnati Children’s patients with FAPD who did – or did not – have anxiety, Dr. Cunningham found that “those who have clinical levels of anxiety don’t respond as well to CBT.” Pain-directed therapy alone, she said, “is insufficient to treat these patients.”

Together with brief screening, stepped therapy delivered via ADAPT offers promise to boost the efficacy of FAPD treatment, perhaps even in a primary care setting, said Dr. Cunningham. She and her collaborators are continuing to study comorbid anxiety and pain in youth; current work is using functional magnetic resonance imaging to examine cognitive and affective changes in patients receiving the ADAPT intervention.

The study was funded by the American Pain Society Sharon S. Keller Chronic Pain Research Grant, Cincinnati Children’s Hospital, and the National Institutes of Health. Dr. Cunningham reported no relevant conflicts of interest.

[email protected]

SOURCE: Cunningham N. et al. APS 2019.

MILWAUKEE – A stepped-care approach to youth with functional abdominal pain disorders may be effective in targeting those with comorbid anxiety, according to ongoing research.

A study of 79 pediatric patients with a functional abdominal pain disorder (FAPD) and co-occurring anxiety found that those who received cognitive behavioral therapy (CBT) that included a component to address anxiety had less functional disability and anxiety than those who received treatment as usual. Pain scores also dropped, though the difference was not statistically significant.

The patients, aged 9-14 years and mostly white and female, were randomized to treatment allocation. Functional disability scores were significantly lower post-treatment for those who received the stepped therapy compared with the treatment as usual group (P less than .05, Cohen’s D = .49). This indicates a moderate effect size, said Natoshia Cunningham, PhD, speaking at the scientific meeting of the American Pain Society.

Mean scores on an anxiety rating scale also dropped below the threshold for clinical anxiety for those receiving the stepped therapy; on average, the treatment as usual group still scored above the clinical anxiety threshold after treatment (P for difference = .05).

The study, part of ongoing research, tests a hybrid online intervention, dubbed Aim to Decrease Anxiety and Pain Treatment, or ADAPT. The ADAPT program includes some common elements of CBT for anxiety that were not previously included in the pediatric pain CBT in use for the FAPD patients, she said.


The hybrid program began with two in-person sessions, each lasting one hour. These were followed by up to four web-based sessions. Patients viewed videos, read some material online, and complete activities with follow-up assessments. The web-based component was structured so that providers can see how patients fare on assessments – and even see which activities had been opened or completed. This, said Dr. Cunningham, allowed the treating provider to tailor what’s addressed in the associated weekly phone checks that accompany the online content.

Parents were also given practical, evidence-based advice to help manage their child’s FAPD. These include encouraging children to be independent in pain management, stopping “status checks,” encouraging normal school and social activities, and avoiding special privileges when pain interferes with activities.

Overall, up to 40% of pediatric functional abdominal pain patients may not respond to CBT, the most efficacious treatment known, said Dr. Cunningham, a pediatric psychologist at the University of Cincinnati. Her research indicates that comorbid anxiety may predict poor response, and that addressing anxiety improves pain and disability in this complex, common disorder.

With a brief psychosocial screening that identifies patients with anxiety, Dr. Cunningham and her colleagues can implement the targeted, partially web-based therapy strategy that tackles anxiety along with CBT for functional abdominal pain.

“Anxiety is common and related to poor outcomes,” noted Dr. Cunningham, She added that overall, half or more of individuals with chronic pain also have anxiety. Among children with FAPD, “Clinical anxiety predicts disability and poor treatment response.”

The first step, she said, was identifying the patients with FAPD who had anxiety, including those with subclinical anxiety.

At intake, children coming to the Cincinnati Children’s Hospital’s gastroenterology clinic complete anxiety screening via the Screen for Child Anxiety Related Emotional Disorders (SCARED) (Depress Anxiety. 2000;12[2]:85-91). Disability and pain are assessed by the Functional Disability Inventory and the Numeric Rating Scale (J Pediatr Psychol. 1991 Feb;16[1]:39-58).

In earlier research, Dr. Cunningham and her collaborators found a significant association between anxiety and both higher pain levels and more disability. And, clinically significant anxiety was more likely among the FAPD patients with persistent disability after six months of treatment.

A surprising finding from the screenings, said Dr. Cunningham, is that youth endorsed more anxiety symptoms in self-assessment than their parents observed. “Children are often their own best informants of their internalizing symptoms,” she said. “Not only do their parents not notice it, it may not be obvious to their providers, either.”

Since many children with FAPD have anxiety, the next question was “How do we better enhance their treatments?” she continued. To answer that question, she took one step back: “How do these youth respond to our current best practice?”

Looking at Cincinnati Children’s patients with FAPD who did – or did not – have anxiety, Dr. Cunningham found that “those who have clinical levels of anxiety don’t respond as well to CBT.” Pain-directed therapy alone, she said, “is insufficient to treat these patients.”

Together with brief screening, stepped therapy delivered via ADAPT offers promise to boost the efficacy of FAPD treatment, perhaps even in a primary care setting, said Dr. Cunningham. She and her collaborators are continuing to study comorbid anxiety and pain in youth; current work is using functional magnetic resonance imaging to examine cognitive and affective changes in patients receiving the ADAPT intervention.

The study was funded by the American Pain Society Sharon S. Keller Chronic Pain Research Grant, Cincinnati Children’s Hospital, and the National Institutes of Health. Dr. Cunningham reported no relevant conflicts of interest.

[email protected]

SOURCE: Cunningham N. et al. APS 2019.

MILWAUKEE – A stepped-care approach to youth with functional abdominal pain disorders may be effective in targeting those with comorbid anxiety, according to ongoing research.

A study of 79 pediatric patients with a functional abdominal pain disorder (FAPD) and co-occurring anxiety found that those who received cognitive behavioral therapy (CBT) that included a component to address anxiety had less functional disability and anxiety than those who received treatment as usual. Pain scores also dropped, though the difference was not statistically significant.

The patients, aged 9-14 years and mostly white and female, were randomized to treatment allocation. Functional disability scores were significantly lower post-treatment for those who received the stepped therapy compared with the treatment as usual group (P less than .05, Cohen’s D = .49). This indicates a moderate effect size, said Natoshia Cunningham, PhD, speaking at the scientific meeting of the American Pain Society.

Mean scores on an anxiety rating scale also dropped below the threshold for clinical anxiety for those receiving the stepped therapy; on average, the treatment as usual group still scored above the clinical anxiety threshold after treatment (P for difference = .05).

The study, part of ongoing research, tests a hybrid online intervention, dubbed Aim to Decrease Anxiety and Pain Treatment, or ADAPT. The ADAPT program includes some common elements of CBT for anxiety that were not previously included in the pediatric pain CBT in use for the FAPD patients, she said.


The hybrid program began with two in-person sessions, each lasting one hour. These were followed by up to four web-based sessions. Patients viewed videos, read some material online, and complete activities with follow-up assessments. The web-based component was structured so that providers can see how patients fare on assessments – and even see which activities had been opened or completed. This, said Dr. Cunningham, allowed the treating provider to tailor what’s addressed in the associated weekly phone checks that accompany the online content.

Parents were also given practical, evidence-based advice to help manage their child’s FAPD. These include encouraging children to be independent in pain management, stopping “status checks,” encouraging normal school and social activities, and avoiding special privileges when pain interferes with activities.

Overall, up to 40% of pediatric functional abdominal pain patients may not respond to CBT, the most efficacious treatment known, said Dr. Cunningham, a pediatric psychologist at the University of Cincinnati. Her research indicates that comorbid anxiety may predict poor response, and that addressing anxiety improves pain and disability in this complex, common disorder.

With a brief psychosocial screening that identifies patients with anxiety, Dr. Cunningham and her colleagues can implement the targeted, partially web-based therapy strategy that tackles anxiety along with CBT for functional abdominal pain.

“Anxiety is common and related to poor outcomes,” noted Dr. Cunningham, She added that overall, half or more of individuals with chronic pain also have anxiety. Among children with FAPD, “Clinical anxiety predicts disability and poor treatment response.”

The first step, she said, was identifying the patients with FAPD who had anxiety, including those with subclinical anxiety.

At intake, children coming to the Cincinnati Children’s Hospital’s gastroenterology clinic complete anxiety screening via the Screen for Child Anxiety Related Emotional Disorders (SCARED) (Depress Anxiety. 2000;12[2]:85-91). Disability and pain are assessed by the Functional Disability Inventory and the Numeric Rating Scale (J Pediatr Psychol. 1991 Feb;16[1]:39-58).

In earlier research, Dr. Cunningham and her collaborators found a significant association between anxiety and both higher pain levels and more disability. And, clinically significant anxiety was more likely among the FAPD patients with persistent disability after six months of treatment.

A surprising finding from the screenings, said Dr. Cunningham, is that youth endorsed more anxiety symptoms in self-assessment than their parents observed. “Children are often their own best informants of their internalizing symptoms,” she said. “Not only do their parents not notice it, it may not be obvious to their providers, either.”

Since many children with FAPD have anxiety, the next question was “How do we better enhance their treatments?” she continued. To answer that question, she took one step back: “How do these youth respond to our current best practice?”

Looking at Cincinnati Children’s patients with FAPD who did – or did not – have anxiety, Dr. Cunningham found that “those who have clinical levels of anxiety don’t respond as well to CBT.” Pain-directed therapy alone, she said, “is insufficient to treat these patients.”

Together with brief screening, stepped therapy delivered via ADAPT offers promise to boost the efficacy of FAPD treatment, perhaps even in a primary care setting, said Dr. Cunningham. She and her collaborators are continuing to study comorbid anxiety and pain in youth; current work is using functional magnetic resonance imaging to examine cognitive and affective changes in patients receiving the ADAPT intervention.

The study was funded by the American Pain Society Sharon S. Keller Chronic Pain Research Grant, Cincinnati Children’s Hospital, and the National Institutes of Health. Dr. Cunningham reported no relevant conflicts of interest.

[email protected]

SOURCE: Cunningham N. et al. APS 2019.

DENVER – Researchers in the early stages of developing an international registry of outcomes in the field of laser surgery have found a lack of uniformity in outcome reporting from existing studies in the medical literature. They’ve also observed insufficient reporting of outcome definitions and under-representation of life impact domains.

“Today, laser therapy is not only an important treatment modality for cosmetic indications, but also for medical skin disorders and diseases,” lead study author Frederike Fransen said at the annual conference of the American Society for Laser Medicine and Surgery. “These disorders include inflammatory lesions, vascular and pigmented lesions, tumors, and scars. Although there are a lot of options for laser therapy, the evidence for most of these skin conditions is quite low, consisting mostly of case reports and case series. However, if we want more evidence-based practice, we need more practice-based evidence.”

A new effort to gain insight into safety and effectiveness of laser treatments known as the international Laser Treatment Dermatology Registry (LEAD) is a platform to address this challenge. “We envision a registry that connects expertise and experience of a large international team of laser specialists, clinicians, and researchers,” said Ms. Fransen, a PhD candidate in the department of dermatology at Amsterdam University Medical Center. “Our goal is to gain insight into safety and effectiveness of laser treatments.” The collaboration includes researchers from the Netherlands, Denmark, France, Germany, Italy, and Switzerland, and the team will be complemented by experts from the United States, Asia, and North Africa.


For the first phase of the endeavor, Ms. Fransen and Albert Wolkerstorfer, MD, PhD, of the University of Amsterdam worked with colleagues from the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) to develop a consensus of outcomes to be included in the registry. This involved a literature review of 350 articles to explore the outcomes used in laser research. From these, the researchers identified 100 articles for outcome mapping: 25 randomized, controlled trials, 44 trials that were not randomized or controlled, and 31 case reports. Their review yielded 98 outcomes and 53 outcome instruments.

Ultimately, outcomes were assigned to eight domains, Ms. Fransen said: appearance, long-term effects, physician-reported physical signs, patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning, and adverse events. Of these domains, the most commonly used in existing medical literature were appearance such as clinical improvement and clearance (81%), followed by adverse effects such as erythema and scarring (55%), physician-reported signs such as morphology (30%), and long-term effects such as recurrence (27%). Ms. Fransen and Dr. Wolkerstorfer observed under-representation of patient-centered outcomes, including satisfaction of appearance or treatment (29%), patient-reported physical signs such as overall state and severity of disease (12%), health-related quality of life (4%), and psychological functioning such as anxiety and depression (1%).

The analysis also revealed that different outcomes measures were used in the various studies, and inconstant definitions within scaling systems. For example, for clearance of lesions/no clearance of lesions, some studies defined excellent clearance as 75% or greater, and others defined marked clearance as 70% or greater. In addition, some studies that used percentage quintile grading as an outcome defined grade 5 as a greater than 95% improvement, while others defined grade 5 as “clear,” or a greater than 90% improvement.

The next step in developing the LEAD registry involves performing an international e-Delphi survey, a method to obtain agreement on outcomes for the registry among health care professionals and patients with different opinions and backgrounds. “The process ends when sufficient agreement is obtained,” Ms. Fransen said. “Looking at future steps, the development of this collaborative initiative with a minimum set of outcomes is essential. When establishing this registry we can achieve sufficient sample size and confirmatory cases toward stronger evidence of laser treatments for orphan diseases.”

The project was supported by the European Academy of Dermatology and Venereology and by an educational grant from ASLMS.

[email protected]

DENVER – Researchers in the early stages of developing an international registry of outcomes in the field of laser surgery have found a lack of uniformity in outcome reporting from existing studies in the medical literature. They’ve also observed insufficient reporting of outcome definitions and under-representation of life impact domains.

“Today, laser therapy is not only an important treatment modality for cosmetic indications, but also for medical skin disorders and diseases,” lead study author Frederike Fransen said at the annual conference of the American Society for Laser Medicine and Surgery. “These disorders include inflammatory lesions, vascular and pigmented lesions, tumors, and scars. Although there are a lot of options for laser therapy, the evidence for most of these skin conditions is quite low, consisting mostly of case reports and case series. However, if we want more evidence-based practice, we need more practice-based evidence.”

A new effort to gain insight into safety and effectiveness of laser treatments known as the international Laser Treatment Dermatology Registry (LEAD) is a platform to address this challenge. “We envision a registry that connects expertise and experience of a large international team of laser specialists, clinicians, and researchers,” said Ms. Fransen, a PhD candidate in the department of dermatology at Amsterdam University Medical Center. “Our goal is to gain insight into safety and effectiveness of laser treatments.” The collaboration includes researchers from the Netherlands, Denmark, France, Germany, Italy, and Switzerland, and the team will be complemented by experts from the United States, Asia, and North Africa.


For the first phase of the endeavor, Ms. Fransen and Albert Wolkerstorfer, MD, PhD, of the University of Amsterdam worked with colleagues from the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) to develop a consensus of outcomes to be included in the registry. This involved a literature review of 350 articles to explore the outcomes used in laser research. From these, the researchers identified 100 articles for outcome mapping: 25 randomized, controlled trials, 44 trials that were not randomized or controlled, and 31 case reports. Their review yielded 98 outcomes and 53 outcome instruments.

Ultimately, outcomes were assigned to eight domains, Ms. Fransen said: appearance, long-term effects, physician-reported physical signs, patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning, and adverse events. Of these domains, the most commonly used in existing medical literature were appearance such as clinical improvement and clearance (81%), followed by adverse effects such as erythema and scarring (55%), physician-reported signs such as morphology (30%), and long-term effects such as recurrence (27%). Ms. Fransen and Dr. Wolkerstorfer observed under-representation of patient-centered outcomes, including satisfaction of appearance or treatment (29%), patient-reported physical signs such as overall state and severity of disease (12%), health-related quality of life (4%), and psychological functioning such as anxiety and depression (1%).

The analysis also revealed that different outcomes measures were used in the various studies, and inconstant definitions within scaling systems. For example, for clearance of lesions/no clearance of lesions, some studies defined excellent clearance as 75% or greater, and others defined marked clearance as 70% or greater. In addition, some studies that used percentage quintile grading as an outcome defined grade 5 as a greater than 95% improvement, while others defined grade 5 as “clear,” or a greater than 90% improvement.

The next step in developing the LEAD registry involves performing an international e-Delphi survey, a method to obtain agreement on outcomes for the registry among health care professionals and patients with different opinions and backgrounds. “The process ends when sufficient agreement is obtained,” Ms. Fransen said. “Looking at future steps, the development of this collaborative initiative with a minimum set of outcomes is essential. When establishing this registry we can achieve sufficient sample size and confirmatory cases toward stronger evidence of laser treatments for orphan diseases.”

The project was supported by the European Academy of Dermatology and Venereology and by an educational grant from ASLMS.

[email protected]

DENVER – Researchers in the early stages of developing an international registry of outcomes in the field of laser surgery have found a lack of uniformity in outcome reporting from existing studies in the medical literature. They’ve also observed insufficient reporting of outcome definitions and under-representation of life impact domains.

“Today, laser therapy is not only an important treatment modality for cosmetic indications, but also for medical skin disorders and diseases,” lead study author Frederike Fransen said at the annual conference of the American Society for Laser Medicine and Surgery. “These disorders include inflammatory lesions, vascular and pigmented lesions, tumors, and scars. Although there are a lot of options for laser therapy, the evidence for most of these skin conditions is quite low, consisting mostly of case reports and case series. However, if we want more evidence-based practice, we need more practice-based evidence.”

A new effort to gain insight into safety and effectiveness of laser treatments known as the international Laser Treatment Dermatology Registry (LEAD) is a platform to address this challenge. “We envision a registry that connects expertise and experience of a large international team of laser specialists, clinicians, and researchers,” said Ms. Fransen, a PhD candidate in the department of dermatology at Amsterdam University Medical Center. “Our goal is to gain insight into safety and effectiveness of laser treatments.” The collaboration includes researchers from the Netherlands, Denmark, France, Germany, Italy, and Switzerland, and the team will be complemented by experts from the United States, Asia, and North Africa.


For the first phase of the endeavor, Ms. Fransen and Albert Wolkerstorfer, MD, PhD, of the University of Amsterdam worked with colleagues from the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) to develop a consensus of outcomes to be included in the registry. This involved a literature review of 350 articles to explore the outcomes used in laser research. From these, the researchers identified 100 articles for outcome mapping: 25 randomized, controlled trials, 44 trials that were not randomized or controlled, and 31 case reports. Their review yielded 98 outcomes and 53 outcome instruments.

Ultimately, outcomes were assigned to eight domains, Ms. Fransen said: appearance, long-term effects, physician-reported physical signs, patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning, and adverse events. Of these domains, the most commonly used in existing medical literature were appearance such as clinical improvement and clearance (81%), followed by adverse effects such as erythema and scarring (55%), physician-reported signs such as morphology (30%), and long-term effects such as recurrence (27%). Ms. Fransen and Dr. Wolkerstorfer observed under-representation of patient-centered outcomes, including satisfaction of appearance or treatment (29%), patient-reported physical signs such as overall state and severity of disease (12%), health-related quality of life (4%), and psychological functioning such as anxiety and depression (1%).

The analysis also revealed that different outcomes measures were used in the various studies, and inconstant definitions within scaling systems. For example, for clearance of lesions/no clearance of lesions, some studies defined excellent clearance as 75% or greater, and others defined marked clearance as 70% or greater. In addition, some studies that used percentage quintile grading as an outcome defined grade 5 as a greater than 95% improvement, while others defined grade 5 as “clear,” or a greater than 90% improvement.

The next step in developing the LEAD registry involves performing an international e-Delphi survey, a method to obtain agreement on outcomes for the registry among health care professionals and patients with different opinions and backgrounds. “The process ends when sufficient agreement is obtained,” Ms. Fransen said. “Looking at future steps, the development of this collaborative initiative with a minimum set of outcomes is essential. When establishing this registry we can achieve sufficient sample size and confirmatory cases toward stronger evidence of laser treatments for orphan diseases.”

The project was supported by the European Academy of Dermatology and Venereology and by an educational grant from ASLMS.

[email protected]

WASHINGTON – The Medicare Payment Advisory Commission will begin work on developing a plan to overhaul the Medicare Part D program.

Gregory Twachtman/MDedge News

Commission members, after hearing about a pair of options related to affordability of specialty drugs and biologics, instructed staff to pursue the option that would essentially amount to an overhaul to the program.

Commission staff presented two options to the commission at a meeting on April 5. Gaining no traction was the easier of the two fixes that could be implemented rapidly – setting a maximum out-of-pocket limit on each specialty tier prescription. The staff used the lesser of a 33% coinsurance (which is generally calculated against the list price of the drug) or $200 for a 30-day supply as the limit.

That first option gained little traction with commission members, who instead gravitated to the option that would restructure the Part D prescription drug benefit to provide stronger formulary and pricing incentives.

As proposed, the second option would replace the coverage gap discount with a manufacturer “cap discount” and restructure the catastrophic benefit.

Commission staff members said that this would help provide stronger incentives for the use of generics, increase affordability for enrollees and the Medicare program, and provide stronger incentives for plans to manage spending. Staff members also said it could provide a disincentive for manufacturers to set high launch prices and/or increase prices rapidly.

The basic plan design would have 25% coinsurance after the deductible is met, up to a to-be-determined out-of-pocket threshold. This would be followed by catastrophic coverage, with details about who pays and how much still to be determined. Currently, the basic structure of the Part D program calls for plan members to pay a 5% coinsurance.

While speaking favorably about the concept of redesign, MedPAC member Kathy Buto, former vice president of global health policy at Johnson & Johnson, noted that it might be a tough sell.

“The difficulty we are going to have, or Medicare will have, in moving to something like this is that people are now entrenched in the current [program],” she said. “As much as I like this, I think it’s daunting moving from the current system.”

She said that if there is a focus on getting the benefits right, it will be a much better approach that could result in lower drug prices.

MedPAC member Amy Bricker, vice president of supply chain strategy at Express Scripts, called for consideration of additional reform to the current program’s six protected classes of drugs, within which plans are required to cover all or substantially all products.

She also suggested providing Part D plans with the ability to exclude high-priced drug launches from their formularies, something they cannot do now.

“Having the ability to exclude a product at launch is the single biggest tool that a commercial plan has and manufacturers fear,” she said, noting that it gives plans leverage, especially if there is little or no competition to that product.

Ms. Bricker came out against the consensus of other members of the commission and supported the out-of-pocket cap in addition to the overhauled Part D proposal.

She noted that the background material provided to the commission offered a suggestion that coinsurance would provide pressure on manufacturers to lower list prices because of the difficulty it puts on beneficiaries. “It doesn’t,” she said. “You can get a headline in the Wall Street Journal. You can hear about these stories in pockets. But it does not impact the decisions of the manufacturer.”

MedPAC staff will be working in the coming year to work out the details of the restructured proposal.

[email protected]

WASHINGTON – The Medicare Payment Advisory Commission will begin work on developing a plan to overhaul the Medicare Part D program.

Gregory Twachtman/MDedge News

Commission members, after hearing about a pair of options related to affordability of specialty drugs and biologics, instructed staff to pursue the option that would essentially amount to an overhaul to the program.

Commission staff presented two options to the commission at a meeting on April 5. Gaining no traction was the easier of the two fixes that could be implemented rapidly – setting a maximum out-of-pocket limit on each specialty tier prescription. The staff used the lesser of a 33% coinsurance (which is generally calculated against the list price of the drug) or $200 for a 30-day supply as the limit.

That first option gained little traction with commission members, who instead gravitated to the option that would restructure the Part D prescription drug benefit to provide stronger formulary and pricing incentives.

As proposed, the second option would replace the coverage gap discount with a manufacturer “cap discount” and restructure the catastrophic benefit.

Commission staff members said that this would help provide stronger incentives for the use of generics, increase affordability for enrollees and the Medicare program, and provide stronger incentives for plans to manage spending. Staff members also said it could provide a disincentive for manufacturers to set high launch prices and/or increase prices rapidly.

The basic plan design would have 25% coinsurance after the deductible is met, up to a to-be-determined out-of-pocket threshold. This would be followed by catastrophic coverage, with details about who pays and how much still to be determined. Currently, the basic structure of the Part D program calls for plan members to pay a 5% coinsurance.

While speaking favorably about the concept of redesign, MedPAC member Kathy Buto, former vice president of global health policy at Johnson & Johnson, noted that it might be a tough sell.

“The difficulty we are going to have, or Medicare will have, in moving to something like this is that people are now entrenched in the current [program],” she said. “As much as I like this, I think it’s daunting moving from the current system.”

She said that if there is a focus on getting the benefits right, it will be a much better approach that could result in lower drug prices.

MedPAC member Amy Bricker, vice president of supply chain strategy at Express Scripts, called for consideration of additional reform to the current program’s six protected classes of drugs, within which plans are required to cover all or substantially all products.

She also suggested providing Part D plans with the ability to exclude high-priced drug launches from their formularies, something they cannot do now.

“Having the ability to exclude a product at launch is the single biggest tool that a commercial plan has and manufacturers fear,” she said, noting that it gives plans leverage, especially if there is little or no competition to that product.

Ms. Bricker came out against the consensus of other members of the commission and supported the out-of-pocket cap in addition to the overhauled Part D proposal.

She noted that the background material provided to the commission offered a suggestion that coinsurance would provide pressure on manufacturers to lower list prices because of the difficulty it puts on beneficiaries. “It doesn’t,” she said. “You can get a headline in the Wall Street Journal. You can hear about these stories in pockets. But it does not impact the decisions of the manufacturer.”

MedPAC staff will be working in the coming year to work out the details of the restructured proposal.

[email protected]

WASHINGTON – The Medicare Payment Advisory Commission will begin work on developing a plan to overhaul the Medicare Part D program.

Gregory Twachtman/MDedge News

Commission members, after hearing about a pair of options related to affordability of specialty drugs and biologics, instructed staff to pursue the option that would essentially amount to an overhaul to the program.

Commission staff presented two options to the commission at a meeting on April 5. Gaining no traction was the easier of the two fixes that could be implemented rapidly – setting a maximum out-of-pocket limit on each specialty tier prescription. The staff used the lesser of a 33% coinsurance (which is generally calculated against the list price of the drug) or $200 for a 30-day supply as the limit.

That first option gained little traction with commission members, who instead gravitated to the option that would restructure the Part D prescription drug benefit to provide stronger formulary and pricing incentives.

As proposed, the second option would replace the coverage gap discount with a manufacturer “cap discount” and restructure the catastrophic benefit.

Commission staff members said that this would help provide stronger incentives for the use of generics, increase affordability for enrollees and the Medicare program, and provide stronger incentives for plans to manage spending. Staff members also said it could provide a disincentive for manufacturers to set high launch prices and/or increase prices rapidly.

The basic plan design would have 25% coinsurance after the deductible is met, up to a to-be-determined out-of-pocket threshold. This would be followed by catastrophic coverage, with details about who pays and how much still to be determined. Currently, the basic structure of the Part D program calls for plan members to pay a 5% coinsurance.

While speaking favorably about the concept of redesign, MedPAC member Kathy Buto, former vice president of global health policy at Johnson & Johnson, noted that it might be a tough sell.

“The difficulty we are going to have, or Medicare will have, in moving to something like this is that people are now entrenched in the current [program],” she said. “As much as I like this, I think it’s daunting moving from the current system.”

She said that if there is a focus on getting the benefits right, it will be a much better approach that could result in lower drug prices.

MedPAC member Amy Bricker, vice president of supply chain strategy at Express Scripts, called for consideration of additional reform to the current program’s six protected classes of drugs, within which plans are required to cover all or substantially all products.

She also suggested providing Part D plans with the ability to exclude high-priced drug launches from their formularies, something they cannot do now.

“Having the ability to exclude a product at launch is the single biggest tool that a commercial plan has and manufacturers fear,” she said, noting that it gives plans leverage, especially if there is little or no competition to that product.

Ms. Bricker came out against the consensus of other members of the commission and supported the out-of-pocket cap in addition to the overhauled Part D proposal.

She noted that the background material provided to the commission offered a suggestion that coinsurance would provide pressure on manufacturers to lower list prices because of the difficulty it puts on beneficiaries. “It doesn’t,” she said. “You can get a headline in the Wall Street Journal. You can hear about these stories in pockets. But it does not impact the decisions of the manufacturer.”

MedPAC staff will be working in the coming year to work out the details of the restructured proposal.

[email protected]